Hypercalcemia in Malignancy

Some Basics

Normal Calcium 2.2 – 2.6 mmol/L To convert mmol/L to mg/dL multiply by 4
Mild Elevation 2.6 – 2.9 mmol/L
Moderate Elevation 2.9 – 3.2 mmol/L
Severe Elevation >3.2 mmol/L
The Correction:
Corrected total calcium = 0.8 (Normal albumin – Measured albumin) + reported calcium

Symptoms “Bone, Stones, Groans”
nocturia (early), polydipsia, polyuria, kidney stones
fatigue, weight loss
headache, irritability, difficulty concentrating, confusion
constipation, obstipation
anorexia, nausea, vomiting, abdominal pain
joint pains, muscle weakness (proximal or general), bone pain

bone/muscle tenderness
mental confusion
reduced deep tendon reflexes
short QT interval, prolonged PR interval on ECG

Why do people with cancer get hypercalcemic?
Two main mechanisms – increased bone resorption, and impaired renal clearance. The mechanisms differ among the different cancers.
Osteoclastic resorption of bone – due to mediators produced either by the tumor cells or by host cells affected by the tumor. Examples: multiple myeloma, breast cancer
Impaired renal clearance – due to parathyroid hormone-related protein PTHrP, a protein that acts as a mediator to increase osteoclastic activity as well as increase calcium reabsorption in the kidney. Has been found in many tumors associated with hypercalcemia. Example: pancreatic cancer

Are different types of cancer more prone to producing hypercalcemic states?
Yes, the type of malignancy is important. Hypercalcemia is common in patients with advanced carcinoma of the breast, but rare in patients with carcinoma of the breast without bone metastases. It is common in squamous cell carcinoma of the lung but rare in small cell carcinoma of the lung. (In fact, it is common in squamous cell carcinomas at any site). It occurs frequently in multiple myeloma, occasionally in the various lymphomas. It occurs occasionally in adenocarcinomas of the kidney, ovary, pancreas, and lung. It is rare in carcinoma of the uterus or colon.

Is this a bad sign?
It is rare for a patient with hypercalcemia of malignancy to live more than 6 months.
Ralston et al. Cancer associated hypercalcemia: morbidity and mortality. Annals of Internal Medicine, 1990; 112(7), 499-504
Hypercalcemia in Malignancy

So how do you treat it?

Pamidronate, 90 mg IV over 4 hours
since its introduction in the early 1990’s, has become a mainstay of treatment.
bisphosphonates are pyrophosphate analogs that act to reduce bone resorption. They have activity against both osteoclasts and osteoblasts, but somehow (mechanism unknown) have a net effect of reducing bone resorption and the dissolution of hydroxyapatite. They are being used for osteoporosis for this reason.
other bisphosphonates include etidronate, alendronate, clodronate

Normal Saline 500-1000 cc IV bolus, then high maintenance rate
Most hypercalcemic patients are volume depleted, and volume depletion leads to a coupled increase of sodium and calcium reabsorption in the proximal convoluted tubules. Saline resuscitation corrects the volume deficit, and increases the calcium excretion by decreasing the coupled sodium and calcium reabsorption.

Lasix 20-40 mg IV q2-4h
This is to help establish a diuresis of > 2500 cc/day and prevent volume overload from the aggressive saline resuscitation. Must be coupled with aggressive normal saline bolus and infusion rate so as to not aggravate volume depletion. Lasix inhibits (albeit weakly) the tubular reabsorption of calcium, but its main purpose is to prevent fluid overload. Do not use thiazide diuretics, as these increase calcium reabsorption and will raise the serum calcium level.

Consider dialysis if serum calcium > 4.5

Also consider:

Inhibits osteoclastic bone resorption and reduces both calcium and phosphate reabsorption in the kidney

Solu-Cortef, 100 mg IV BID
Not really useful for acute hypercalcemia
Antagonizes vitamin D, thereby

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